In recent years, it has been shown that enzymes can be used to alleviate certain disorders of the blood by reducing the amount of a particular substrate within the blood. The blood is contacted with an enzyme which degrades the substrate whose concentration it is desirable to reduce. However, the administration of an enzyme to a patient by injection into the blood stream of the patient makes control of the total enzyme activity difficult because it is impossible to limit the time period during which the enzyme acts on the substrate. In addition, certain free enzymes have toxic side effects making injection difficult or unfeasible.
To avoid these toxic side effects, many attempts have been made to immobilize the enzyme on an insoluble support and then pass an extracorporeal blood flow over this support. This approach seeks to permit the enzyme to act on the substrate while preventing release of the enzyme into the blood stream and the accompanying undesirable side effects.
Attempts made in the past to immobilize biochemically active enzymes on or within various types of support materials have met with varying degrees of success. Among the problems encountered are short shelf life for the support-bound enzyme, leakage of enzyme from the support, a low enzyme holding capacity for certain supports, incompatibility with a blood flow because of such problems as platelet aggregations, and reduced enzyme activity because of excessive bonding to the enzyme or interference of substrate and enzyme product flow through the support. Excessive activation of the support by a linking agent increases the probability of multiple site bonding on the enzymes which quite frequently results in substantial deactivation of the enzyme. Certain prior methods of retaining enzymes on a support have also resulted in large increases in apparent K.sub.M, the apparent Michaelis constant, indicating a substantial decrease in substrate affinity.
Accordingly, it would be desirable to provide a reactor or device which avoids or minimizes the deficiencies of the prior art and provides a biochemically active enzyme that remains active after being stably retained by a matrix. The bio-artificial organ of the present invention meets the foregoing requirements.